The present invention relates to non-toxic polymeric compositions containing an organosulfide antioxidant and, more particularly, to such compositions which are adapted for the handling and packaging of foods, beverages or pharmaceuticals, or for use in medical devices.
In general, all plastics have a tendency to degrade or deteriorate, particularly when exposed to air or oxygen at elevated temperatures. The degree to which a polymer will degrade will vary from polymer to polymer. Upon thermal and oxidative degradation, plastics tend to become discolored and brittle, which detracts from their usefulness. In order to stabilize polymers against the deleterious effects of thermal and oxidative degradation, it is known in the art to incorporate small amounts of various phenolic, arylamine, phosphite, or sulfide antioxidants, alone or in combination.
U.S. Pat. Nos. 3,180,850, 3,258,493, 3,293,209, and 3,574,165 all teach the use of antioxidants as ingredients in polyolefin resins to protect the resins against both thermal and oxidative degradation.
U.S. Pat. Nos. 3,652,680 and 3,772,246 disclose certain cycloalkane bis(alkyl sulfides) for use in polyolefins as antioxidant synergists. These patents also report that these compounds have low toxicity, which is of value when used in polyolefin bottles and film for packaging materials. For example, beta-(n-octadecylthio) ethyl-3 (and 4)-(n-octadecylthio)cyclohexane was found to be non-toxic when administered orally to mice at doses as high as 10 grams per kilogram of body weight (g/kg).
Commonly assigned copending application Ser. No. 07/429,885, filed Oct. 31, 1989, which is hereby incorporated by reference, discloses substituted and unsubstituted alkylthiopropyl ethers suitable for use as antioxidants for polyolefin resins.
Commonly assigned copending application Ser. Nos. 07/429,889 and 07/429,883, both filed on Oct. 31, 1989, and 07/698,235, filed May 6, 1991, all of which are hereby incorporated by reference, disclose the use of three classes of sulfide antioxidants as thermal and oxidative stabilizers for engineering and cross-linked polyolefin resins. These sulfide antioxidants include the above referenced alkylthiopropyl ethers, bis [alkylthiopropyl(substituted and unsubstituted)] ethers, and cycloalkane bis- and tris(alkyl sulfides).
Antioxidants are also used with the styrenic resins, which includes both crystalline and non-crystaline homopolymers; expandable polystyrene beads; rubber-modified polystyrenes, such as high impact polystyrene (HIPS), medium impact polystyrene (MIPS), and super high impact polystyrenes; and block copolymers of styrene and butadiene, such as styrene-butadiene (SB), styrene-butadiene-styrene (SBS) and butadiene-styrene-butadiene (BSB). A further description of these resins may be found in the articles by N. L. Maecker and D. N. Armentrout in the "Encyclopedia of Polymer Science and Engineering", 2nd Ed., Vol. 16, pp. 179-193 (1989) and G. Riess, G.Hurtrez, and P. Bahadur, ibid., Vol 2, pp. 324-434 (1989).
Unsaturated polyesters are still another class of resins which may require antioxidants to improve stability at high use temperatures. These resins are generally prepared by reacting a mixture of diacids and/or anhydrides, in which at least one component is unsaturated, with a glycol to form a mixture of saturated and unsaturated diesters. This mixture is then dissolved in an unsaturated monomer, such as styrene, which is then cross-linked under free radical conditions to form a thermoset. The article by J. Selley in the "Encyclopedia of Polymer Science and Engineering", 2nd Ed., Vol. 12, pp. 256-29 1988 describes these resins in more detail.
Polymeric compositions are useful in the manufacture of textiles, coatings, packaging and molded articles. A major application area is in the production of coatings and packages for storing and handling of foods, beverages, and pharmaceuticals, and as components of medical devices that come in contact with body fluids. When used in these applications, the polymeric compositions, as well as the articles made therefrom, need to be "non-toxic" or safe for use by consumers for their intended purpose. These compositions and their components generally require the approval of appropriate health-regulatory agencies, such as the U.S Food and Drug Administration (USFDA).
In order for a material to qualify as a "food grade" (as defined by the USFDA) additive, it must not present any toxicity hazard at the highest use level at which it will be present in the food packaging material. The criteria for determining whether a given ingredient in a plastic material constitutes a toxicity hazard have been defined by the USFDA. These criteria are set forth in a comprehensive article that appeared in the October, 1955 issue of the Food Drug Cosmetic Law Journal, and can be summarized as follows:
(1) An ingredient of a plastic material which is not extracted by a foodstuff with which it is in contact does not constitute a hazard.
(2) If a material is found in a food as a result of contact with the plastic, that material may constitute a hazard if it is toxic in a biological sense, i.e., if it causes either an acute or chronic injurious effect by oral ingestion, inhalation, or absorption through the skin, in animal or humans. If no such effect can be shown, the material does not constitute a hazard.
(3) Acute toxicity levels are unlikely ever to be realized in practice. It is, however, possible that injurious effects may be produced by repeated small doses of a material extracted from the plastic and therefore it is the chronic toxicity which should be used for purposes of assessing the hazard.
(4) The toxicity hazard of a material is a function both of its chronic toxicity as well as its extractability from the plastic under service conditions.
(5) For the purpose of assessing the hazard, extractability studies must be carried out using the foodstuffs themselves or a range of representative extractants under conditions which simulate the most severe conditions likely to be encountered in practice. The results of these tests must be combined with the data on chronic toxicities of the plastic as expressed by their Toxicity Factors to give the Toxicity Quotient, which is a measured of the hazard.
To have a composition approved by the USFDA and other national health authorities as a food grade additive, an applicant must submit data from feeding studies on laboratory animals which demonstrates that the daily consumption of a candidate composition over an extended period of time at concentration levels above those that would be expected based on extractability of the composition from the packaging material does not noticeably impair the health of the animals or result in a sufficient accumulation in the blood, bones, and internal organs.
Prior to the enactment of the regulations concerning food grade additives, dilauryl and distearyl thiodipropionate antioxidants were approved by the USFDA for use in the manufacture of food packaging materials under 21 CFR 181.24. These thiodipropionate antioxidants did not undergo the rigorous test procedures now required by the USFDA for food grade additives. Distearyl and di(2,4 di-t-butylphenyl) pentaerythritol diphosphites have also been granted USFDA approval for use as antioxidants and/or stabilizers for polymers used in the manufacture of food packing materials (21 CFR 178 2010). The former diphosphite has approval for use in olefin polymers, polystyrene, and rubber-modified polystyrene, while the latter phosphite has approval for use in polyolefins.
Both thiodipropionate and the phosphite antioxidants are known in the art to suffer from hydrolytic instability due to the ester functionality. Sulfide antioxidants used in non-USFDA applications generally possess hydrolytic stability, but may contain one or more mercaptan-containing impurities, which are known in the art to impart highly obnoxious odors even when present at low levels in the stabilizer. Thus, there is a need for hydrolytically stable sulfide antioxidant for use in polymeric compositions, which are adapted for the handling and packaging of foods, beverages or pharmaceuticals, or for use in medical devices, having a low order of toxicity and being substantially free of obnoxious odors.